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Objectives.Overweight/obesity has been implicated to play a role in cognitive deficits in bipolar disorder (BD). This study aims to identify the relationship between body fat distribution and different domains of cognition in BD during euthymia.Methods.A sample of 100 euthymic individuals with BD was measured with a cognitive test battery (i.e., Trail Making Test-A-B/TM-A/B, d2 Test of Attention, Stroop test, California Verbal Learning Test/CVLT) and an anthropometric measures set (body mass index, waist circumference, hip circumference, waist-to-hip-ratio, waist-to-height-ratio, and lipometry). Patient data were compared with a healthy control group (n =64).Results.Results show that overweight patients with BD exhibit lower performance in the TMT-A/B as well as in the free recall performance of the CVLT compared to normal-weight patients with BD and controls. In bipolar individuals, (abdominal) obesity was significantly associated with a poor cognitive performance. In bipolar females, associations with measures of verbal learning and memory were found; in bipolar males, associations with poor performance in the TMT-A/B and in the Stroop interference task were demonstrated. In controls, no associations were found.Conclusions.There are several possible pathways moderating the association between obesity and cognition in BD. Anthropometric and lipometry data underline the substantial mediating impact of body fat distribution on cognition in BD. [ABSTRACT FROM AUTHOR]

Purpose: Respiratory-guided computed tomography (CT) typically employs breathing motion surrogates to feed image reconstruction or visual breathing coaching. Our study aimed to assess the impact of table movements and table sag on the breathing curves recorded in four-dimensional (4D) CT and deep-inspiration breath-hold (DIBH) CT., Methods: For breathing curve measurements, static and dynamic phantom scenarios were used. Breathing curves were recorded using three different surrogate systems and the impact of table sag due to weights of up to 130 kg was analyzed and compared to a non-weighted setting, respectively. The calibration procedure of the system used as an input for the visual coaching device used for clinical DIBH CT scans was adapted. We evaluated corresponding breathing curves acquired during DIBH and 4DCT scans of altogether 70 patients using various stability metrics., Results: The various surrogate systems showed consistent table sag measurements below 4 mm, even under loads up to 130 kg, compared to a reference scan conducted without additional weight. Higher weight loads were related to steeper table sag fall-offs towards the deepest table position. For DIBH CT scans, the visual guidance was heavily affected by artifacts. This resulted in breathing threshold limits, which could not be achieved by 48% (n = 21) of the, respectively, examined patients. Using the new calibration workflow, the baseline drift was compensated better and 90% (n = 20) of the addressed patients stayed within the thresholds. The evaluated table sag in clinical 4DCT scans (n = 29) stayed below 3 mm compared to the non-weighted situation., Conclusion: Table movement and sag can impact breathing curves recorded by different surrogate systems. Correcting table movement and sag artifacts is crucial for reliable breathing curve acquisition in respiratory-guided CT., (© 2024 The Author(s). Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Background and Purpose: Model-based dose calculation considering tissue compositions is increasingly being investigated in brachytherapy. The aim of this study was to assess the suitability of modern cone-beam computed tomography (CBCT) imaging compared to conventional computed tomography (CT) scans for this purpose., Materials and Methods: By means of a phantom study, we evaluated the CT numbers and electron densities measured using a modern CBCT device as well as a conventional CT scanner for various materials. Based on this, we compared dose calculations (using the TG-43 formalism as well as model-based collapsed cone calculations assuming uniform materials [ACE uniform ] and considering CT numbers [ACE CT# ]) on planning CTs and control CBCTs for patients with cervical and breast cancer as well as phantom-simulated skin cancer cases. Assessing dosimetric deviations between the planning CTs and control CBCTs acquired during the treatment course served to estimate interfractional implant variations., Results: The comparison of ACE uniform -ACE CT# deviations between planning CTs and control CBCTs revealed no statistically significant difference for almost all examined dose parameters. Dosimetric deviations between model-based dose calculations and TG-43 were partly significant but of small magnitude (< 10 cGy per fraction). Interfractional dosimetric variations were substantially larger than the dosimetric differences found between the various dose calculation procedures., Conclusion: Model-based dose calculation based on modern CBCT imaging was suitable. However, the found differences between these calculations and the TG-43 formalism should be investigated in dose-outcome analyses. The observed interfractional dosimetric variations revealed the importance of performing treatment quality assurance., Competing Interests: Conflict of interest: A. Karius, M. Shariff, S. Schaller, M. Lotter, V. Strnad, N. Lackner, R. Fietkau, C. Bert, R. Merten and C. Schweizer declare that they have no competing interests. Research agreements with Elekta and medPhoton companies regarding ImagingRing applications in brachytherapy exist but were not directly related to the present work., (© 2024. The Author(s).)

Understanding and optimising biological pre-treatment strategies for enhanced bio-methane production is a central aspect in second-generation biofuel research. In this regard, the application of fungi for pre-treatment seems highly promising; however, understanding the mode of action is crucial. Here, we show how aerobic pre-treatment of crystalline cellulose with the cellulolytic Trichoderma viride affects substrate degradability during mesophilic, anaerobic digestion. It could be demonstrated that fungal pre-treatment resulted in a slightly reduced substrate mass. Nevertheless, no significant impact on the overall methane yield was found during batch fermentation. Short chain organic acids accumulation, thus, overall degradation dynamics including methane production kinetics were affected by the pre-treatment as shown by Gompertz modelling. Finally, 16S rRNA amplicon sequencing followed by ANCOM-BC resulted in up to 53 operative taxonomic units including fermentative, syntrophic and methanogenic taxa, whereby their relative abundances were significantly affected by fungal pre-treatment depending on the duration of the pre-treatment. The results demonstrated the impact of soft rot fungal pre-treatment of cellulose on subsequent anaerobic cellulose hydrolysis as well as on methanogenic activity. To the best of our knowledge, this is the first study to investigate the direct causal effects of pre-treatment with T. viride on basic but crucial anaerobic digestion parameters in a highly standardised approach., (© 2024 The Author(s). Environmental Microbiology Reports published by John Wiley & Sons Ltd.)

Lithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extracellular matrix (ECM), and PI3K-Akt signaling networks were associated with response to lithium. In this study, we replicated the results of our previous study using network propagation methods in a genome-wide association study of an independent sample of 2039 patients from the International Consortium on Lithium Genetics (ConLiGen) study. We identified functional enrichment in focal adhesion and PI3K-Akt pathways, but we did not find an association with the ECM pathway. Our results suggest that deficits in the neuronal growth cone and PI3K-Akt signaling, but not in ECM proteins, may influence response to lithium in BD., (© 2024. The Author(s).)

Mutations in the COL7A1 gene lead to malfunction, reduction or complete absence of type VII collagen (C7) in the skin's basement membrane zone (BMZ), impairing skin integrity. In epidermolysis bullosa (EB), more than 800 mutations in COL7A1 have been reported, leading to the dystrophic form of EB (DEB), a severe and rare skin blistering disease associated with a high risk of developing an aggressive form of squamous cell carcinoma. Here, we leveraged a previously described 3'-RTMS6m repair molecule to develop a non-viral, non-invasive and efficient RNA therapy to correct mutations within COL7A1 via spliceosome-mediated RNA trans -splicing (SMaRT). RTM-S6m, cloned into a non-viral minicircle-GFP vector, is capable of correcting all mutations occurring between exon 65 and exon 118 of COL7A1 via SMaRT. Transfection of the RTM into recessive dystrophic EB (RDEB) keratinocytes resulted in a trans -splicing efficiency of ~1.5% in keratinocytes and ~0.6% in fibroblasts, as confirmed on mRNA level via next-generation sequencing (NGS). Full-length C7 protein expression was primarily confirmed in vitro via immunofluorescence (IF) staining and Western blot analysis of transfected cells. Additionally, we complexed 3'-RTMS6m with a DDC642 liposomal carrier to deliver the RTM topically onto RDEB skin equivalents and were subsequently able to detect an accumulation of restored C7 within the basement membrane zone (BMZ). In summary, we transiently corrected COL7A1 mutations in vitro in RDEB keratinocytes and skin equivalents derived from RDEB keratinocytes and fibroblasts using a non-viral 3'-RTMS6m repair molecule.

Objective . There is a continuous increase in 3D printing applications in several fields including medical imaging and radiotherapy. Although there are numerous advantages of using 3D printing for the development of customized phantoms, bolus, quality assurance devices and other clinical applications, material properties are not well known and printer settings can affect considerably the properties (e.g. density, isotropy and homogeneity) of the printed parts. This study aims to evaluate several materials and printer properties to identify a range of tissue-mimicking materials. Approach . Dual-energy CT was used to obtain the effective atomic number ( Z eff ) and relative electron density (RED) for thirty-one different materials including different colours of the same filament from the same manufacturer and the same type of filament from different manufacturers. In addition, a custom bone equivalent filament was developed and evaluated since a high-density filament with a composition similar to bone is not commercially available. Printing settings such as infill density, infill pattern, layer height and nozzle size were also evaluated. Main results . Large differences were observed for HU (288), RED (>10%) and Z eff (>50%) for different colours of the same filament due to the colour pigment. Results show a wide HU variation (-714 to 1104), RED (0.277 to 1.480) and Z eff (5.22 to 12.39) between the printed samples with some materials being comparable to commercial tissue-mimicking materials and good substitutes to a range of materials from lung to bone. Printer settings can result in directional dependency and significantly affect the homogeneity of the samples. Significance . The use of DECT to extract RED, and Z eff allows for quantitative imaging and dosimetry using 3D printed materials equivalent to certified tissue-mimicking tissues., (Creative Commons Attribution license.)

Since the start of the 2019 pandemic, wastewater-based epidemiology (WBE) has proven to be a valuable tool for monitoring the prevalence of SARS-CoV-2. With methods and infrastructure being settled, it is time to expand the potential of this tool to a wider range of pathogens. We used over 500 archived RNA extracts from a WBE program for SARS-CoV-2 surveillance to monitor wastewater from 11 treatment plants for the presence of influenza and norovirus twice a week during the winter season of 2021/2022. Extracts were analyzed via digital PCR for influenza A, influenza B, norovirus GI, and norovirus GII. Resulting viral loads were normalized on the basis of NH 4 -N. Our results show a good applicability of ammonia-normalization to compare different wastewater treatment plants. Extracts originally prepared for SARS-CoV-2 surveillance contained sufficient genomic material to monitor influenza A, norovirus GI, and GII. Viral loads of influenza A and norovirus GII in wastewater correlated with numbers from infected inpatients. Further, SARS-CoV-2 related non-pharmaceutical interventions affected subsequent changes in viral loads of both pathogens. In conclusion, the expansion of existing WBE surveillance programs to include additional pathogens besides SARS-CoV-2 offers a valuable and cost-efficient possibility to gain public health information.

Objectives: Many factors influence the outcome of in vitro antifungal susceptibility testing (AFST), including endpoint definition, inoculum sizes, time and temperature of incubation, and growth medium used. This European Confederation of Medical Mycology (ECMM) Excellence center driven study investigated multiple colony testing (MCT) of five separate colonies to investigate the prevalence of polyresistance (PR), defined as heterogeneous MICs from a same-species Candida culture irrespective of the underlying resistance mechanism., Methods: Candida spp. MCT for fluconazole and anidulafungin was performed by Etest prospectively comprising 405 clinical samples. MCT results were compared to the real-life routine MIC data and PR was assessed. Candida colonies displaying strong PR were selected for genotyping using multilocus sequence typing and random amplified polymorphic DNA assays for C. lusitaniae., Results: Candida PR was observed in 33 of 405 samples (8.1%), with higher rates for non-albicans species (26/186, 14%) than for C. albicans (7/219, 3.2%), and for fluconazole than for anidulafungin. MCT detected acquired resistance more often than routine AFST (18/405, 4.5%) and 9 of the 161 investigated blood cultures showed PR (5.6%). Multilocus sequence typing and random amplified polymorphic DNA did not reveal a uniform genetic correlate in strains studied., Conclusions: This study shows that Candida single MIC-values obtained in routine diagnostics may be incidental, as they fail to detect PR and resistant subpopulations reliably. The reasons for PR seem to be manifold and should be regarded as a phenotypical expression of genomic variability irrespective of the underlying resistance mechanism, which may help to interpret ambiguous and non-reproducible AFST results., (Copyright © 2022. Published by Elsevier Ltd.)

Purpose: The Local Effect Model version one (LEM I) is applied clinically across Europe to quantify the relative biological effectiveness (RBE) of carbon ion beams. It requires the full particle fluence spectrum differential in energy in each voxel as input parameter. Treatment planning systems (TPSs) use beamline-specific look-up tables generated with Monte Carlo (MC) codes. In this study, the changes in RBE weighted dose were quantified using different levels of details in the simulation or different MC codes., Methods: The particle fluence differential in energy was simulated with FLUKA and Geant4 at 500 depths in water in 1-mm steps for 58 initial carbon ion energies (between 120.0 and 402.8 MeV/u). A dedicated beam model was applied, including the full description of the Nozzle using GATE-RTionV1.0 (Geant4.10.03p03). In addition, two tables generated with FLUKA were compared. The starting points of the FLUKA simulations were phase space (PhS) files from, firstly, the Geant4 nozzle simulations, and secondly, a clinical beam model where an analytic approach was used to mimic the beamline. Treatment plans (TPs) were generated with RayStation 8B (RaySearch Laboratories AB, Sweden) for cubic targets in water and 10 clinical patient cases using the clinical beam model. Subsequently, the RBE weighted dose was re-computed using the two other fluence tables (FLUKA PhS or Geant4)., Results: The fluence spectra of the primary and secondary particles simulated with Geant4 and FLUKA generally agreed well for the primary particles. Differences were mainly observed for the secondary particles. Interchanging the two energy spectra (FLUKA vs. GEANT4) to calculate the RBE weighted dose distributions resulted in average deviations of less than 1% in the entrance up to the end of the target region, with a maximum local deviation at the distal edge of the target. In the fragment tail, larger discrepancies of up to 5% on average were found for deep-seated targets. The patient and water phantom cases demonstrated similar results., Conclusion: RBE weighted doses agreed well within all tested setups, confirming the clinical beam model provided by the TPS vendor. Furthermore, the results showed that the open source and generally available MC code Geant4 (in particular using GATE or GATE-RTion) can also be used to generate basic beam data required for RBE calculation in carbon ion therapy., (© 2022 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

The cofactor F 420 is synthesized by many different organisms and as a redox cofactor, it plays a crucial role in the redox reactions of catabolic and biosynthetic metabolic pathways. It consists of a deazaflavin structure, which is linked via lactate to an oligoglutamate chain, that can vary in length. In the present study, the methanogenic Archaea Methanosarcina thermophila and Methanoculleus thermophilus were cultivated on different carbon sources and their coenzyme F 420 composition has been assayed by reversed-phase ion-pair high-performance liquid chromatography with fluorometric detection regarding both, overall cofactor F 420 production and distribution of F 420 glutamyl tail length. In Methanosarcina thermophila cultivated on methanol, acetate, and a mixture of acetate and methanol, the most abundant cofactors were F 420 -5 and F 420 -4, whereby the last digit refers to the number of expressed glutamyl rests. By contrast, in the obligate CO 2 reducing Methanoculleus thermophilus the most abundant cofactors were F 420 -3 and F 420 -4. In Methanosarcina thermophila, the relative proportions of the expressed F 420 tail length changed during batch growth on all three carbon sources. Over time F 420 -3 and F 420 -4 decreased while F 420 -5 and F 420 -6 increased in their relative proportion in comparison to total F 420 content. In contrast, in Methanoculleus thermophilus the relative abundance of the different F 420 cofactors remained stable. It was also possible to differentiate the two methanogenic Archaea based on the glutamyl tail length of the cofactor F 420 . The cofactor F 420 -5 in concentrations >2% could only be assigned to Methanosarcina thermophila. In all four variants a trend for a positive correlation between the DNA concentration and the total concentration of the cofactor could be shown. Except for the variant Methanosarcinathermophila with acetate as sole carbon source the same could be shown between the concentration of the mcrA gene copy number and the total concentration of the cofactor., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

We evaluated the newly proposed agar screening method for echinocandin susceptibility testing of 144 Aspergillus section Terrei isolates compared with the Etest method. Both methods defined the isolates to be wild-type strains for anidulafungin and micafungin, with Etest minimal effective concentrations (MECs) of ≤0.004 mg/L. For caspofungin, the novel agar screening method identified 37 isolates to be caspofungin non-wild type based on their fluffy colony appearance on caspofungin agar. Etest MECs for caspofungin for these isolates were scattered widely from 0.002 to 0.750 mg/L, showing only partial accordance between the two methods.

Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) raises concerns as to whether it contributes to an increased mortality. The incidence of CAPA varies widely within hospitals and countries, partly because of difficulties in obtaining a reliable diagnosis. We implemented a routine screening of respiratory specimens in COVID-19 ICU patients for Aspergillus species using culture and galactomannan (GM) detection from serum and/or bronchoalveolar lavages (BAL). Out of 329 ICU patients treated during March 2020 and April 2021, 23 (7%) suffered from CAPA, 13 of probable, and 10 of possible. In the majority of cases, culture, microscopy, and GM testing were in accordance with CAPA definition. However, we saw that the current definitions underscore to pay attention for fungal microscopy and GM detection in BALs, categorizing definitive CAPA diagnosis based on culture positive samples only. The spectrum of Aspergillus species involved Aspergillus fumigatus , followed by Aspergillus flavus , Aspergillus niger , and Aspergillus nidulans. We noticed changes in fungal epidemiology, but antifungal resistance was not an issue in our cohort. The study highlights that the diagnosis and incidence of CAPA is influenced by the application of laboratory-based diagnostic tests. Culture positivity as a single microbiological marker for probable definitions may overestimate CAPA cases and thus may trigger unnecessary antifungal treatment.